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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Constitutive Activation of the Nutrient Sensor mTORC1 in Myeloid Cells Induced by Tsc1 Deletion Protects Mice from Diet-Induced Obesity

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Paschoal, Vivian A. [1] ; Belchior, Thiago [1] ; Amano, Mariane T. [2] ; Burgos-Silva, Marina [2] ; Peixoto, Albert S. [1] ; Magdalon, Juliana [1, 3] ; Vieira, Thayna S. [1] ; Andrade, Maynara L. [1] ; Moreno, Mayara F. [1] ; Chimin, Patricia [4] ; Camara, Niels O. [2] ; Festuccia, William T. [1]
Total Authors: 12
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508000 Sao Paulo - Brazil
[3] Israelita Albert Einstein Hosp, BR-05652900 Sao Paulo - Brazil
[4] Univ Estadual Londrina, Phys Educ & Sports Ctr, Dept Phys Educ, BR-86051990 Londrina, Parana - Brazil
Total Affiliations: 4
Document type: Journal article
Web of Science Citations: 2

Scope: To test whether myeloid cells Tsc1 deletion and therefore constitutive activation of the nutrient sensor mTORC1 protects from high-fat diet (HFD)-induced obesity, glucose intolerance, and adipose tissue inflammation. Methods and results: Mice with Tsc1 deletion in myeloid cells (MTsc1KO) and littermate controls (MTsc1WT) were fed with HFD for 8 weeks and evaluated for body weight, glucose homeostasis, and adipose tissue inflammation. MTsc1KO mice were protected from HFD-induced obesity and glucose intolerance. MTsc1KO, however, displayed, independently of the diet, abnormal behavior, episodes of intense movement, and muscle spasms followed by temporary paralysis. To investigate whether obesity protection was due to myeloid cells Tsc1 deletion, bone marrow was transplanted from MTsc1WT and MTsc1KO into irradiated C57BL6/J mice. Mice transplanted with MTsc1KO bone marrow displayed reduced body weight gain, adiposity, and inflammation, and enhanced energy expenditure, glucose tolerance and adipose tissue M2 macrophage content upon HFD feeding, in the absence of abnormal behavior. In vitro, Tsc1 deletion increased in a mTORC1-dependent manner macrophage polarization to M2 profile and mRNA levels of fatty acid binding protein 4 and PPAR gamma. Conclusion: Constitutive mTORC1 activation in myeloid cells protects mice from HFD-induced obesity, adipose tissue inflammation, and glucose intolerance by promoting macrophage polarization to M2 pro-resolution profile and increasing energy expenditure. (AU)

FAPESP's process: 11/10783-7 - mTOR complex 1 involvement in the control of macrophage function in the chronic inflammatory response associated with obesity and insulin resistance
Grantee:Vivian Almeida Paschoal
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches
Grantee:Niels Olsen Saraiva Câmara
Support type: Research Projects - Thematic Grants
FAPESP's process: 09/15354-7 - Role of adipose tissue in the development of obesity and associated co-morbidities: investigation of molecular mechanism and search for alternative therapies
Grantee:William Tadeu Lara Festuccia
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 15/19530-5 - Involvement of the nutrient sensor mTOR in the development of obesity associated chronic metabolic diseases
Grantee:William Tadeu Lara Festuccia
Support type: Research Projects - Thematic Grants